A cell scattering factor has been isolated from the conditioned media of human embryo lung fibroblasts. This factor is assayed using either human mammary epithelial cells obtained from human milk samples or using a dog kidney epithelial cell line (MDCK). This assay measures the disassociation of the desmosomes between epithelial cells grown as islands in monolayers. This factor has a molecular weight of approximately 55,000 daltons and is a heat and acid labile protein (see Stoker, M., J. Cell. Physiol., 121:174-183 (1984); Stoker, M. et al., J. Cell Sci., 77:209-233 (1985) and Stoker, M. et al, Nature 327:239-242 (1987)).
A cell scattering factor has also been isolated from a human melanoma cell line (A2058). This factor is assayed using a human melanoma cell line (A2058) as indicator cells for the presence of the factor. This assay measures chemotaxis of the human melanoma cell line (A2058) (see Liotta, L. A. et al, Proc. Natl. Acad. Sci., USA, 83:3302-3306 (1986)). This cell scattering factor is thought to be the same factor as that described by Stoker, M., J. Cell. Physiol., 121:174-183 (1984); Stoker, M. et al. J. Cell Sci., 77:209-233 (1985) and Stoker. M et al, Nature, 327:239-242 (1987).
The observations that transformed cells grow as loosely associated clumps of cells and the normal rat kidney (NRK) colonies induced by the combination of epidermal growth factor (hereinafter "EGF") and tumor growth factor (hereinafter "TGF")-.beta. consist of tightly associated aggregates of cells, suggested that there might be other ectopic factors released by transformed cells that were able to confer a loose colony morphology and that such factors might play a role in determining the metastatic potential of transformed cells.
Using the above rationale, i.e., that ectopic factors released by tumor cells can contribute to their expressed phenotypes, clones of a human metastatic tumor cell line were selected for a loose colony morphology, expecting that the colonies with loose morphologies would be producing factors that contributed to the expressed morphology.
As a result, it was ascertained that one clone. i.e., M3827 clone 3 (ATCC No. CRL 9193) released a factor that was able to induce a loose colony morphology in a normal rat kidney fibroblast clone (NRK-49F) (ATCC No. CRL 1570). This factor has been designated tumor egress factor or egressin and has been found to coelute with a factor possessing EGF-like activity (TGF-.alpha.) having an apparent molecular weight of 25,000 daltons in 1.0M acetic acid. (See DeLarco, J. E. et al, Proc. Natl. Acad. Sci., USA, 82:5015-5019 (1985) and DeLarco, J. E. et al, Molecular Cell Biology, 5:101-106 (1987).)
Inflammatory cells such as monocytes and granulocytes also are believed to move between cell compartments, disrupting cell junctions and exhibiting increased motility. Thus, a supernatant from a human monocyte cell line (U937) (ATCC No. CRL 1593), activated into the microphage differentiation pathway, was examined in the present invention for egressin-like activity. It has been ascertained in the present invention that this cell line also produces egressin.